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Dr. Mark Hyman
Coming up on this episode of the Dr. Hyman Show.
Dr. Eric Topol
When you start talking about preventing Alzheimer's and picking it up early, how early can you start to see the P TAU changes?
Mark
P Tau217 is the very first one that goes up and it starts 20 years before mild cognitive impairment. 20 years.
Dr. Mark Hyman
Dr. Eric Topol is a world renowned.
Mark
Physician using data tech and deep insight.
Dr. Mark Hyman
To transform how we detect and prevent diseases like Alzheimer's before they even start.
Mark
There's so much data to show that that social isolation is a risk factor for neurodegenerative and cardiovascular and even cancer.
Dr. Eric Topol
Strength training is a powerful drug and sleep is a powerful drug. They're better than most of the drugs we have. Actually.
Dr. Mark Hyman
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Dr. Eric Topol
Welcome back to the podcast, Dr. Topols. Good to have you again.
Mark
Thanks Mark. Good to be with you.
Dr. Eric Topol
Last time, you know, we talked a lot about AI and health and medicine and got into some pretty cool topics. Since then you've written a book called Super Agers, which I think is a great, a great title. When you start talking about preventing Alzheimer's and picking it up early, how early can you start to see the P tau changes, for example, or the proteomic clocks change in someone? Is it, is it five years before they get symptoms? Is it 10, 20 years? Yeah.
Mark
I'm so glad you get.
Dr. Eric Topol
How much do we know about that?
Mark
P Tau217 is the very first one, one that goes up and it starts 20 years before mild cognitive impairment. 20 years. I mean, it's incredible.
Dr. Eric Topol
That's pre. That's pre dementia.
Mark
Yeah. Yeah. I mean, you got another few years from when you go from MCI to actual Alzheimer's.
Dr. Eric Topol
Yeah. It reminds me of this patient I had who had APOE 4 and that's the high risk Alzheimer's gene. It doesn't mean you're going to get it, but it really dramatically increased your risk. She was a patient of Mine at Canyon Ranch like 25 years ago. And she was in her 90s, she was a dentist, she was still working and she had been a health nut her whole life. Here she was in her 90s, completely cognitively intact. Not sure I'd want her to be my dentist at 95, but still she was, she was all there. And I was like, wow. It was a very, it was one of those memorable patients that, you know, teach you a lesson about what's possible. And I was like, wait, just because you have a genetic risk doesn't mean you're going to get the disease. Like everybody in my mother's side of the family, on her dad's side, all had severe heart disease in their 50s, heart attacks, you know, bypasses and so forth. You know, I thought, oh boy, I'm going to, I'm going to be in trouble. But turns out that, you know, they might have a predisposition, but they're not predestined. You kind of started, I think, and you can correct me if I'm wrong down this road by doing this study of elderly people who you end up calling welderly, which were people that lived a long time and you dove into a lot of things, genetics, lifestyle. And I would love you to sort of unpack some of the myths that got busted there because I think everybody thinks that, you know, there's a longevity gene or if you just, you know, had a good hand dealt you with your genetic cards, that you, you're going to live a long time and if you don't, you're kind of stuck with whatever you got, you know, oh, my father got heart disease, my mother had diabetes, my grandma got Alzheimer's. I'm just kind of destined to be getting some disease in the future. But you kind of found some surprising things when you do this study. Can you, can you unpack that study a little bit what you found and what was surprising about it?
Mark
So it was called the Welderly study. And it took seven years to find 1400 people who were average age near 90 and up to 102 who had never had had a chronic illness, age related or otherwise. So it was, you know, very unique cohort that has not yet ever been replicated in terms of that type of demographic. And we did whole genome sequencing on all of them and surprisingly we thought we'd find, as you said, all these genetic underpinnings and we found almost nothing. This is also consistent with so many of these people had relatives like the patient I present in the book, Lee Russell, who is 98 and her parents died in their 50s and 60s, her brothers the same. And so it isn't a genetic story. And for many people like myself with a terrible family history, it's quite liberating. But of course some of its genetics, but for the most part it's much less than we thought. It was a big surprise to us. It was a disappointment because we thought we're going to find all these important and it's really in contrast to the elderly, which is, as you know, elderly.
Dr. Eric Topol
I like that, I like that. Elderly.
Mark
The elderly are the people over 60. They have all these chronic age related diseases. The contrast is striking. And the genetic story is much less important than I think we had forecasted. And also of course, if you talk to these people, they really did take care of themselves. They really had good lifestyles. I think we learned a lot from them.
Dr. Eric Topol
Can you talk a little bit about that? Because that's part of what your work is really focused on is the polygenic risk, which means what are the patterns of genes that put you at risk but don't necessarily make you predestined?
Mark
Yeah, that's really important that you're bringing up because there are several studies I review in the book of polygenic risk and how that's neutralized by lifestyle factors. That's another way to support what we found in the elderly. Whatever genetic load there is or burden that there's ways to titrate that by taking care of ourselves. But there's another point that's really interesting. Some of the people in that worldly group did not take care of themselves. I remember one fellow 99 years old who was still smoking two packs a day.
Dr. Eric Topol
Wow.
Mark
Nothing of course is 100%, but there's a lot to titration of risk with, you know, really good lifestyle behaviors. But there's another factor here. Whether it's random or whether I do think as I get into it later in the book, our immune system is so critical and that is giving us that resilience to withstand the threat of age related diseases. And, and I think we're only scratching the surface right now because clinically we don't have a way to get the metrics of our immune system. We're just starting to do that now and we need to really get something that would be part of our assessment, whether it's annual checkup or whatever, particularly as we get older. As you well know, we have this problem with immunosenescence or immune system starting to really let our guard down as we get older. And it's highly variable. Some people it's entirely intact all the way through their 90s. And other people, it's already starting to lose some of its integrity in their 50s and 60s.
Dr. Eric Topol
Yeah. So, so a lot of what people think of as the normal age related diseases, heart disease, cancer, diabetes, dementia, these are all inflammatory diseases and they, they, there's a term for this called inflamma. Aging.
Mark
Yes.
Dr. Eric Topol
And that we tend to get more inflamed as we get older. So on one hand our immune system works less well to fight against infections, but the other hand it's overactive and causing inflammation. And I think, you know, one of the things you talk about in the book is your, your epigenetic clocks, biological clocks. And how do the, how do we look at organ clocks and overall clocks? And you know, I was thinking about the other day, it was occurred to me that when we measure a lot of the biological clocks, we do it through a blood test.
Mark
Yeah.
Dr. Eric Topol
And the cells we're looking at, because there's no cells except for white blood cells because red cells have no nucleus and no DNA. So white blood cells are the things we're actually measuring these clocks on. So are we actually indirectly measuring our immune age?
Mark
Yeah. So this is really important that the epigenetic methylation clock, that is a body wide assessment of biological age. But it doesn't, as you say, it doesn't get to the crux of the matter. And so that's why it's so exciting are these protein or proteomic scores where you take up to 11,000 plasma proteins and you get eight organ clocks including the immune system. So brain, heart, liver, kidney. This is really great because now this can be done very inexpensively. We're doing it in our research these days and the costs for us have come down from what was 8 or $900 to less than $100. And the Biobank UK Biobank is doing it for $50 for in 500,000 people. They've already done it in 50 some thousand. And so when you have those protein clocks with AI writes out what's tagged to each organ, that's getting at your point, Mark, because it's no longer relying on just some white cells. It's actually getting to the crux of the proteins that are associated with each organ. So it's our first cut of a way to inexpensively get a readout on the aging of each organ and also our immune system. And that's, I think that's a breakthrough and it's going to be part of our routine assessment in patients going forward. And it's critical to me, the science of aging has brought these things forward. Not just these ideas of reversing aging with fancy things like partial epigenetic reprogramming or senolytics or telomeres lengthening and all kinds of stem cells, but rather the metrics that have come in these recent years like organ clocks and other things we'll talk about. That's what's so exciting. Giving us this real opportunity to prevent age related diseases like we've never done before.
Dr. Eric Topol
Yeah, I just want to unpack that because it's so important. I don't, I'm sure most people will get it. So normally when we look at biological age, quote, biological age and the way it's been measured in the past has been by looking at your, your genes and the epigenome, which is basically the control mechanism over your genes that determines which genes get turned on or off or expressed. And, and we're looking at patterns in that epigenome that give us a sense of your biological age. And that's kind of an expensive, somewhat non specific way to check. But you're talking about this new technology using the tens of thousands of proteins in our blood that can be measured very easily and cheaply that show patterns that can give you clues about the specific rate of aging of different organs in your body, Is that right?
Mark
Yeah. And that's the key because it's not just, you know, with polygenic risk score or genome sequencing or things like, you know, Apoe 4 that you mentioned that just said, that just told us yes or no, that just told us you may be at risk for this type of cancer or Alzheimer's, whatever. Now we're getting at the point of not just what organ, but when. So the three major age related diseases take more than 20 years. Cancer for almost all cancers, cardiovascular and certainly Alzheimer's. Neurodegenerative, they take more than 20 years. And we've never really been able to get on top of that with all this Runway that we have to work with. It's incredible.
Dr. Eric Topol
And so, yeah, you're right.
Mark
You know, now we have a way to be ahead of it and that these metrics, these ways of seeing what, in what person, what organ, if, if one is aging too fast out of pace with that person and also what is the trajectory or arc of that. So this is, I think, an opportunity that we've never had before and it's, it's a really big advance.
Dr. Eric Topol
Yeah, I mean you, you, you're a Cardiologist, So you, you were taught in, you know, plumbing 101 basically and wait, waiting till things happen. And yes, you could give a statin, but that's a very, you know, kind of, I would say, weak tool. I mean, it's a tool, but you know, the benefits, marginal. Like it's not like a panacea or a magic pill.
Mark
Yeah, it works well, you know, someone's already had a heart attack. Secondary prevention, but we're not making big inroads. There's still plenty of people having heart attacks and bypass surgery and stents and everything else. So we have to do better. And as you know, cardiovascular is the most preventable of these three diseases. 80, 90%, our colleagues, former colleagues from Cleveland Clinic came out with that's 90%, others 80%. But then cancer and neurodegenerative are 40, 50% preventable through lifestyle. So we know some things even without these new metrics and new capabilities to be able to prevent these diseases, we're just not doing it.
Dr. Eric Topol
And did you find out in that study of the elderly, what were those things that you found? What was surprising? What did you sort of see that you were surprised at or unexpected?
Mark
Well, it was interesting, the disposition of these people. Almost all of them remarkably upbeat people. You did not see people that were complaining or misanthropes or anything like that. You know, they had a relatively sunny disposition like the Lee Russell and the other fellow who I present in the book, two patients of mine, they were kind of prototypic. So that's one thing. You know, it's hard to, there's not hard science on personality and being optimistic. Of course they're very grateful for how well they've healthily aged. But it's more than that. They've been that way, you know, throughout their lives. They, they're physically active. You know, they're not, they're not sitting around. I remember when I was getting back in touch with my 98 year old, she's so busy with her art gallery oil painting, it was hard to get her, you know, an appointment to go visit her. You know, so these, these people, they stay busy, they stay active, they're, they're not socially isolated, they don't live in a cave, you know, and they're relatively thin. You know, you don't see much obesity in people who are in well into their 90s, who have staved off any major age related disease. So they have a profile that's pretty typical among this group. And they're, they're not common. I Mean really? It took seven years to find this cohort, so. Yeah, yeah, you know, we're talking about well, less than 1% of people in that age group.
Dr. Eric Topol
Yeah, I mean less common in America. I was in Sardinia and Korea and you see more of those people who are fit and thin and healthy and happy. I mean, yeah, it's true. I think optimists live longer even if they're wrong. That's the good news.
Mark
The mental health. Yeah.
Dr. Eric Topol
I call myself a pathological optimist. I don't know why, but I seem to see the life of Brian. You'll look on the bright side of life. It's kind of a funny thing, Monty Python Skip. But I think that mindset plays a big role and I think we underestimate the role of our beliefs and our mindset and our view of the world and our level of gratitude, our level of service or engagement or connection to other people. They seem like squishy things, but I think they are really consequential.
Mark
Yeah, no, I had a whole chapter on mental health because of its primacy here in the interactions with physical health and how stressed anxiety, depression, you know, is a key to these age related diseases, how we, how we deal with that. And as you touched on earlier, this whole inflammation story is the common thread of the big three age related diseases. And you know, we know that stress can induce that anxiety. So any way that we can keep that inflammation low and of course that's going to be very much a factor of what we eat and our exercise and sleep health and all that. So there's so many things, it could be environmental toxins, burden that have that effect on inflammation but we never should underestimate our mental health for that factor.
Dr. Eric Topol
I was reading a lot about sociogenomics years ago and this whole idea that how our social relationships, connections affect our gene expression. And I remember seeing these studies where they looked at people who were in relationship, if they had a conflictual relationship, they were turning on inflammatory genes and gene expression. If they had loving heart centered connections, they would have anti inflammatory genes turned on. And I think that's kind of worth noting that it may not be hard science, but I think although that was pretty good science, I was really just this idea that we should not neglect our relationships. And often I think what happens in people's lives is they work hard, have their career, their family, they go and go, go and they, they neglect their social relationships and their networks and they end up like retiring or stopping and they have like, where are their friends and who, who are the people they can call up. And the amount of loneliness and disconnection is a big factor, no question.
Mark
And you know, that was a graph that a lot of people have highlighted in the book about how as we age we tend to become recollusive. And there's so much data to show that, that social isolation is a risk factor for neurodegenerative and cardiovascular and even cancer. So we want to avoid that. And I think highlighting that social interaction, I mean we are really a social animal. We have to use that ability to help us stay in the mix. And so this is something I was impressed with that research. I would have been one to discount it, but when I went through it all, it really was cogent.
Dr. Eric Topol
You talked about the polygenic risk score and that it increases your risk, but it doesn't necessarily guarantee you're going to get a problem. There's a lot we know about how to modify that risk. I mean, I'm wondering the smoker, you mentioned it earlier, who smoked two packs a day. Just as there's the Apoe 4 4, which is the high risk Alzheimer's and heart disease gene, the double two I've heard some people refer to as the jackpot gene. That's like you can smoke and drink and eat whatever you want and you kind of won the genetic lottery and you don't have to worry as much. Was there anything to that? Were there any parts of that?
Mark
Well, if you want to pick apoe2 homozygote, that's pretty good. But it doesn't give you the ability to withstand age related diseases. It gives you longevity. So that's the difference here that we're talking about health span versus lifespan. And so Apoe 2 double is the one you want to get. And of course I got, I got.
Dr. Eric Topol
One copy, I got one copy.
Mark
Good for you. And in fact, when I go through genome editing, there's a whole chapter in the book where people are editing Apo turning Apoe 4 to Apoe 2 right now. I mean.
Dr. Eric Topol
Oh wow.
Mark
Yeah, I mean it's wild and in animals and you know, the idea of to do this in people, that may happen someday, who knows. But right now, Apoe 2, no question that it does. Unlike Apoe 4, it has a better associated lifespan, but it doesn't give you that age related protection from these three diseases. Really.
Dr. Eric Topol
What also I think was important in your book is you do talk about the difference between this health span lifespan distinction. We spend the last 20% of our lives in poor health and do what you want and you're engaged and you feel good, right? And what's the point of living a long life if you feel like crap for the last 20% of your life, right? Or you're taking a pile of pills? How did they kind of, kind of make that almost the same in this wealthy group? How is their lifespan, healthspan the same?
Mark
There's a couple of things here we've got to do something about this elderly that you're framing because that's what we have now. That's, that's basically the story. And most people, and they as they get in during the 60s and 70s, they have at least one of these three if not more age related major diseases that is compromising their health span and it may indeed their lifespan as well. But you know, living with one of these major diseases, whether it's mild cognitive deficit, moving on to Alzheimer's or one of these cancers that you're trying to be a survivor fighting it, or certainly all the cardiovascular disease issues that crop up, heart failure and arrhythmias and everything else, this isn't easy. This is not the life you want. What I think is so extraordinary is we're at a time where we have the means of squashing these, preventing these diseases like we never had. So why accept this the way we've been all these years with this highest density of age related disease people, when we have the stack, the full stack now, it isn't just polygenic risk score or sequencing which we could get, it's also become very inexpensive, but it's all these other layers of data that we've been talking about. The point about that is, let's say the polygenic risk score is wrong or off a bit. You've got all these other checkpoints of layers and then you have multimodal AI to bring it all together. And so that's what gives us that pinpoint precision, both with respect to time, you know when this is going to be cropping up way in advance. And that's when we get all over these people to work with them to prevent the disease. And of course that could be the lifestyle plus factors, or it could be drugs and other means and even more high tech ways to go into surveillance. So we have a path to do this for the big three diseases. We just got to get moving on.
Dr. Eric Topol
I want to unpack that because there's a lot there you said. I want to just ask you a question though, before we dive into the big three, which is heart disease, cancer and dementia. You left out diabetes. I'm wondering why you left that out. Yeah, it's sort of the cause of all three of those.
Mark
Well, that's right. Diabetes by itself, we can handle that. But the problem with diabetes is it leads to the other three. The other three are the biggest ones we have to work with. And diabetes isn't necessarily age related. There's some of that, but it's not nearly like the other three. And it doesn't have the 20 year lead time to work with. So there's a lot of reasons why. Although diabetes is considered a killer, certainly can compromise health span, it's mainly working through the other three. You know, people are not dying diabetes, but they're dying of the heart related kidney. You know, other sequela, certainly more dementia and more cancer too. That's why I don't lump it in there. But I think the prototype is Alzheimer's. You saw I wrote in the book. And then also a substack, there's this breakthrough test, the P Tau to 17.
Dr. Eric Topol
Yeah.
Mark
And if you are Apoe 4, I mean if you're a carrier, that's 20, 25% of us are carriers, or you have a family history of Alzheimer's, or both. You probably want to get a P Tau 217 because it's as good as cerebral spinal fluid. It's as good as a pet cow scan, you know, which is a lot of radiation and hard to get.
Dr. Eric Topol
And CT scan in the brain, but it's expensive and hard to get.
Mark
Yeah. And here you got a blood test which is not that expensive. It's available in this country for the past two years. And you know, Mark, most people never heard of it. I think it's part of your function tests that you do.
Dr. Eric Topol
It is, it is, yeah. I added that.
Mark
Yeah. I don't know all the tests that you do in that, but that one is a good one. So then, you know, you have, if you have. I don't recommend everybody getting this, but if you have APOE 4 and you have family history now, you know, with the P Tau test and you can get a brain clock. Okay. You can even get a methylation clock. You got these layers of data now, right. And you also know about your lifestyle and what's good and what's not so good about it. Now you find, oh, P Tau 217 is elevated substantially, let's say, well, this is like an LDL cholesterol, Right. Because if you exercise and you go into a healthy lifestyle, you can bring it down. And we've seen a randomized study presented here in San Diego, at the Academy of Neurology annual meeting, where they had these. The people who had P Tau 217 elevated, they. They were randomly assigned to intervention with lifestyle. And it came way down. You know, P217, P Tau181, all these markers, 75, up to 75% reduction. That should reduce or, you know, the chances of ever developing Alzheimer's, particularly if it started early. And then, of course, if the person started late, it should put it off, should defer it. So this is exciting, and I'm just amazed that most people don't know about this test.
Dr. Eric Topol
No, I agree. I want to just double down on that because what you're saying is so revolutionary. Up till now, basically, you had a family history of Alzheimer's. You had to cross your fingers and wait around and hope to not get it. And there wasn't anything we offered from medicine that was going to prevent it or even treat it once you got it. So it was kind of a scary thing. And nobody wanted to know their APOE status because it's like, well, why should I know? Because what am I going to do about it?
Mark
Yeah.
Dr. Eric Topol
And I think, you know, what we've learned is that now with early biomarker testing, and like you said, these develop 20, 30, 40 years before you ever forget something. Right. You forget your keys or you start having memory loss, you can start to see these early clues in your blood, and you layer on top of that proteomics, you layer on top of that AI to uninterpret it all. And all of a sudden, you have a window into where you might be headed that you could do something about. And I think trials like the Finger trial and the Pointer trial are these large clinical trials that show while all the drugs we have for Alzheimer's have failed, the lifestyle interventionists can slow, prevent, slow, and even reverse sometimes the changes that we see. And I think Richard Eisen's work's very exciting about, about P Tau 270, because it's like you can actually start to see how we can actually even reverse it once you start to have it, which is pretty good.
Mark
Yeah, that's what's the difference where we were a few years ago to where we are now is that we know that these markers are so accurate and we can use them to see if we're making progress. Okay, so you have the, let's say the brain organ clock and the P Tau217 and someone who clearly has high risk of Alzheimer's. And you go six months with this new Lifestyle, Right. And you see, oh wow, the brain pace of aging is slowing down and the P Tau 217 has come down 50%. You say this is working and if you want you can do imaging course. But this is extraordinary because now we have the GLP1 drugs like ozempic, Mounjaro that are being tested in big Alzheimer's trial in thin people. You know, these are not obese or overweight.
Dr. Eric Topol
Yeah.
Mark
These are thin people and because they have such potency of reducing brain inflammation. So we're not talking about the drugs that are being used for Alzheimer's which don't work very well and are very risky and can cause hemorrhage in the brain. These are drugs that have been out there, you know, 20 some years. You know, I have a whole chapter in the book is how we blew it. We thought they were only good for diabetes, you know, and it took right, right. This scientist in Denmark, Latte Knudsen, who kept pushing, we have to try it, we have to try it in obesity. And they kept saying to her, well Latte, it's not going to work because the diabetes, the diabetics only lose three or four pounds. Well now we see they we can get people to lose, you know, 40, 50, 60, 80 pounds. These drugs are so potent and the reason we admit we it was blown was because the diabetics don't lose that weight. And we don't know why still today, which is such a mystery. Right. But what if it works in Alzheimer's? Because it's working in so many other ways in terms of addiction, in terms of all these other cardiovascular many conditions that we did not expect. So even if it doesn't work, there's other drugs, many other drugs that get well into the brain, that knock down brain inflammation like GLP1. And so we're going to have drugs for people who are at high risk for Alzheimer's to add to the lifestyle factors. But of course you want to press on the lifestyle stuff first before you ever really start with drugs.
Dr. Mark Hyman
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Dr. Eric Topol
So, so you're, you're someone who's listening. You go get this test, you know you're in your 40s, shows up as something that's a little bit elevated. What do you do?
Mark
Yeah, well, first don't get the test unless you have the risk factors. Right? I mean you don't really want to get this without APOE4 status or at least Alzheimer's in your family. Right. Because. Or a polygenic risk score even that says you're high risk for Alzheimer's. Something like that. Because if you get tests that are not, you don't have a high test pre the probability as you know you're going to get potentially false positives. And the American Alzheimer's association, which I think has some problems, they're labeling people with P Tau 217 as stage one Alzheimer's. If it's elevated, that's not good because it could be wrong. Any test could be wrong, especially if it's done on the wrong people. So as long as admonishing that get the test only if you have increased risk. And if it's elevated, then you go on and go on a campaign to bring it down. And know since you're saying a person's Young, in their 40s or 50s, they got lots of time to really get on it. And you know, within a few years we're going to have a lot more additional ways to bring that down. But just, I mean the lifestyle story, it's hard to get people to adopt all these healthy behaviors particularly get isn't just a behavior. How do you get a lot more deep sleep, for example, a lot more sleep regularity which has big impact. That's not even a behavior, that's just something that people, they have to learn how to improve. The fact when you get into this aggressive prevention mode, it's more likely that people are going to take it seriously if they have this marker aligned with their risk.
Dr. Eric Topol
So in terms of the lifestyle, that's a, that's sort of a generic term. But let's kind of break it down. Diet, exercise, sleep, stress, relationships, I mean toxins, you call it lifestyle plus.
Mark
Yeah.
Dr. Eric Topol
You know, what are the biggest levers to pull?
Mark
Well, we start with diet. You know, I think you've been on this. But the ultra processed food are just horrendous, right. They are the vectors of inflammation in our body and they are propagating. They are in, I think we're talking about cause and effect of these three age related diseases. And the US has the highest consumption in the world, 70% plus. And of course a lot of people are 80% or more. And in the book, you know, I review.
Dr. Eric Topol
Yeah, that's average. That's average.
Mark
Yeah, yeah. Children high, very high. I reviewing the book, my friend Chris Van Tulleken who wrote the book Ultra Processed People and you know he went on like a 30 day and he's a really great physician scientist in the UK and well he, it told the whole story. He had a brain scan beforehand, he had all these inflamed inflammation markers beforehand. And in 30 days, kind of like super size Me, he tried to go as high as he could on ultra processed food. By the time the 30 days was up, his brain was all inflamed. Every biomarker had gone through the ceiling of abnormality for inflammation. I mean it was just 30 days of this bad diet. He gained 20 pounds. Now this is, this is a something we have to work on. It's just we've done nothing in this country to bring it down. Other countries are taking it more seriously. The second thing about the diet which I think is vital is the protein craze. We have people out there that are advocating ridiculous amounts of protein and I review that in the book, that there's danger with that not only for the kidneys but also we've seen studies after studies that show too high a protein diet, particularly animal protein, can induce, promote atherosclerosis. That's the last thing we want. Right. It's pro inflammatory. So that's why, although it's probably wise if we keep up a decent amount of protein, maybe amp it up a bit as we get older, you know, maybe 1.2, 1.4 or so per kilogram, not per pound. And that's what some people are advocating and that's just wrong. It's dangerous. There's no data to support it. You know, I talk to people who are in this protein craze and I try to get them onto the data and the evidence which is, you know, really a danger sign if they go too high on a daily and it's not going to increase their muscle mass. When you go past good studies, 1.5, 1.6 per kilogram. So that's, those are a couple of the main things. I don't know what you think about that, but a couple of main things about the diet that we need to get out there.
Dr. Eric Topol
And the sugar, the sugar in the starch too? Oh yeah, A component of the ultra processed food. But I think that's part of the driver of what's causing a lot of the problem. And yeah, it is. You know they're calling Alzheimer's type 3 diabetes. Right. Diabetes of the brain. I think that's, that's a big factor for people. It's the amount of sugar and starch and it's, it's obviously hidden in the ultra processed food. Yeah, I think the protein thing's interesting. I mean, I think. What were you going to say? Something about the sugar thing?
Mark
Oh no, I think I agree with you. I reviewed the sugar story. Salt, caffeine, alcohol. We went through every one of these things. Everything you eat, fats and plant based diets and red meat. And I went through the whole thing. And you're familiar with this recent study of 105,000 people followed 30 years and only 9% of them, only 9% got to the elderly state past age 7. And those 9%, what did they eat? They mainly play it plant based foods, Mediterranean diet, some but small amounts of red meat. You know, the kinds of things you, you would anticipate where the data evidence is back backing it up. So, yeah, the diet is really important and we keep seeing study after study reinforcing that.
Dr. Eric Topol
I think one of the things that's important, as you know, is, is being functional and frailty is the killer. I mean, hip fractures is a bigger risk for death than getting a diagnosis of cancer. That muscle mass is a big deal.
Mark
Yeah.
Dr. Eric Topol
And the question is, that's a problem as you get older, because when you lose it and it's hard to build it, and there's something called anabolic resistance, meaning when you're older, it takes a lot more work and a lot more protein to do the same thing you did when you had these trophic or growth hormone like things when you were younger, anabolic hormones that were floating around your blood. And, and the Protege group, which is a group of protein scientists led by Don Layman and others, and I've had him on the podcast, he talks about even higher amounts being needed, like, you know, one up to, you know, one and a half to two grams per kilo. And, and this was like a, I'm not a protein expert, but it was interesting to read their, their data showing that, that it's, it was this, this to overcome this resistance and they need to maintain muscle mass. That their data was, was like the kind of global think tank on, I don't know, protein experts.
Mark
Well, I reviewed all that data and I would just say, you know, if you're going to go past 1.51 person per kilogram, you're starting to get to a fuzzy zone. But, but Mark, you can increase your muscle mass not by just, you know, having adequate protein, by doing strength training. Strength training. And I, I got into that heavy be over the last year because after all the research, you know, I always advocated aerobic exercise as a cardiologist, you know, cardiologists, right. These people, patients would come in and they were really cut and buffed and I'd say, well, what are you doing? All these weights, Right? Well, now I'm doing that. Not, not maybe as trying to be any like the Terminator, but, you know, I've been on a big kick on, you know, resistance and strength training, balance, posture, you know, but also, I've never been this strong in my life and I don't, I don't need crazy amounts of protein. The point being is, yeah, it's part of the exercise. It isn't like you just change your diet and you build up muscle. Right. It's the exercise. So essential. And by the way, the data for resistance training, as I review in the book with various graphs. It's extraordinary for preventing age related the big three. So we should be doing that. I learned from that. I didn't realize how impressive that body of data was.
Dr. Eric Topol
Yeah, you and me both. When I was 59, I'm like, yeah, I better start strength training. And it's changed my life and my body. I have pictures of me when I'm 40 and I was a runner, I was into yoga. I wasn't overweight, but like my body looked like I was like a skinny little rail compared to now. I'm not like, you know, the Terminator or the rock, but I'm like, you know, at 65, beefier than I've ever been in my whole life. Yeah. And yeah, I was like, wow, this.
Mark
Is for me, it's the same crazy.
Dr. Eric Topol
That's possible.
Mark
I think this is a really important step. And then the other biggie is of course the deep sleep story and regularity. I mentioned it earlier. We need to get as we get older and going along, as you said with the inflammation is that we don't get enough sleep as we get older, particularly the slow wave deep sleep. And we've got to get that up. When I started looking at that data, I was horrified because I'm not a very good. I had not been a good sleeper and I started tracking it with a ring and a smartwatch and I'm saying, wow, I'm getting less than 15 minutes of deep sleep a night, you know, and terrible overall scores of my sleep because of that. And so I started finding out what is causing all this problem. Right. And because I had very, you know, irregular times of going to sleep, you know, erratic and what I ate, what I drank, when I exercise, you know, when I ate. All these factors were playing such a big role. Now I've been able to get. It's rare that I wouldn't get over 45 minutes a night, even up to an hour. So it's been a big difference. So I know that.
Dr. Eric Topol
What did you do? Oh, I were the things that made a difference.
Mark
Yeah. So all these things cumulatively by tracking learning, like for example, not exercising too late in the day, not eating too late in the day, you know, in the evening. Interestingly, alcohol affects many people with respect to deep sleep. But that one didn't seem to have too much of an effect on me. Avoiding drinking too much of fluids and then avoiding having to get up interrupted sleep made a big difference during the night because I always be hydrating, you know, in the evenings. No, don't hydrate all Day long but don't hydrate in the evening. So lots of things that I did but you know, the timing and also certain foods, you know, I was basically, I wasn't aware of it but you know, is the, the indigestion was interrupting sleep somehow. So certain foods and also I think there's these interactions, you know, stress and things that we all deal with. I learned about a better coping mechanisms to get sleep and I'd still like to amp it up more because that data that I review in super ages, it's very impressive the, the link between the deep sleep which is when we get rid of the toxic waste metabolites in our brain. That's the time. And by the way, I know we both see patients that take Ambien and other sleep medicine and what's interesting is that they backfire. Not only do they not get rid of the waste, but they actually increase. Ambien especially been noted to increase the waste that stay in the brain. So you, the person may feel like they're getting more sleep, but they're not. And of course along the way I didn't have it but certainly one of the concerns I had with that low amount of deep sleep was did I have sleep apnea? Was that the issue? And that fortunately wasn't the case. But as you know, that's a common problem that doesn't get diagnosed.
Dr. Eric Topol
So it sounds like writing the book helped you live longer because you learn all these things, I don't know, like you hadn't known before. But those are powerful drugs. I mean strength training is a powerful drug and sleep is a powerful drug. Yes, they're better than most of the drugs we have.
Mark
Actually it did, it helped me but of course I wasn't going to. Once I reviewed all the evidence and I was, I felt compelling, that led me to change my ways and I'm hoping that's going to help a lot of other people too. But I don't know if it's going to make my, make me into the elderly. I, with my family history, it's always in my mind, despite our worldly trial that our study that, you know, I may not get into the. So far I fit. I don't have any age related chronic disease and I hope I can go another, you know, 10, 20 years. See.
Dr. Eric Topol
Well, I think you're a few years older than me and if you've escaped those diseases by now, you probably kind of dodged the bullet.
Mark
I hope so. I, I mean, but the main thing is I wanted to get the hard evidence out There I wanted to get so people know that there is a huge body of evidence that is not Brian Johnson, don't die or other longevity clinics that charge $250,000 that do hyperbaric chambers, plasma phoresis, all these putative anti aging supplements, none of which have any data, you know, all this kind of reckless use of things. I wanted to just put it out there that hey, this is what we know and it can make a world of difference. And a lot of this stuff is not very expensive either, you know, so that was the real purpose of doing the book. And I just as a, as a outgrowth, it helped me too.
Dr. Eric Topol
Yeah. I think the things that work the best cost the least, you know. Yeah. Eating well doesn't have to be very expensive. Exercising is basically free, you know, getting sleep and optimizing your sleep is basically free.
Mark
Yeah.
Dr. Eric Topol
Building relationships, connections, pretty much free, you know. And yes, there may be things around the margin where we're going to learn in the future that maybe plasma phoresis helps or maybe, you know, stem cells might help or maybe some of these in, you know, things that are under investigation now like rapamycin may help. Yeah, but, but right now the, the, the, the, their edge, Their edges, not the, the core of what people should be doing.
Mark
Yeah.
Dr. Eric Topol
Calls it majoring in the minors and minoring in the majors, you know, and I think that's a very good way to think about it. Live a crappy lifestyle and take those drugs and things and actually think you're going to do much.
Mark
No, and all these things that people are, you know, trying to advance, like the rapamycin story, that they're, they have a danger too. We can't measure the immune system, you know, routinely. So why are we taking an immunosuppressant drug which in some people could be a big deal. And, and if you look at this leaderboard of all the, the longevity researchers or influencers, they're all taking different doses. It's like once a week, different dose, once a day, nobody knows. But it's never been shown to have any benefit in people. It's all in, you know, rodents.
Dr. Eric Topol
Yeah. There was one trial I saw that was on elderly and they found that if it was given intermittently, it actually improved their response to vaccines and, and actually help their immune system function better, whereas continuous dosing didn't. And I, I think there's MTOR1 and MTOR2, which have different roles and immunity. And so I mean, I mean that story's still getting unpacked, but I, I find it interesting. But it, but again it's like, it's like if you don't do the basics right, that still doesn't matter.
Mark
Right. We don't know of any studies, you know, that are real. Those are these small studies that in limited number of people they're not major endpoint. But you know, one thing that's interesting, Mark, is you know Steve Horvath who had came up with the Horvath clock, we were talking about that epigenetic. The only two things so far that have decreased biologic aging from that clock are exercise and then more recently the GLP1 drug. I mean that's kind of interesting. That's body wide biologic aging. What we haven't seen any studies that, that's been accomplished through, you know, these other things like rapamycin. So I welcome, I mean if rapamycin works or metformin or whatever, I'm, I, I want these things to succeed, but I don't want people to jump to that unless we have the evidence because all these carry some risk. I mean metformin carries less risk than, than rapamycin because it doesn't cause immunosuppression. But it isn't something that we know is going to promote healthy aging.
Dr. Eric Topol
But it does, it does inhibit mitochondrial complex 1, which worries me because yeah, with progressive resistance training compared to placebo with and without metformin. If you did a strength training with metformin, you didn't get the same response to building muscle which really got like. I was like, oh boy. Yeah, that's not a good thing. I think so, yeah, they may be.
Mark
Like, you're making a good point. You really are.
Dr. Eric Topol
This is really exciting. So basically Alzheimer's and dementia, the take home is there's biomarkers now that we can detect early. Both genetic risks combined with blood tests that give us an early indication that we should get on it. And then the getting on it part. There's a lot of things we can do. Lifestyle plus all the things we talked about. And there's more for sure that we could unpack. So I want to kind of get to the other ones. Heart disease and this is your area specialty.
Mark
Yes. But I just want to mention one thing. You know, it's kind of chasing our tails. But the environment, in terms of air pollution, in terms of microplastics, nanoplastics and also of course forever chemicals. These things are, you know, all three are inflammation inducers that are increasing our toll of age related diseases. The, the big three and diabetes too for that matter. So, you know, we're not doing enough about these. And, and I think this is something that you've been working on for quite some time. We got to get serious about this because the, any advances that we're going to make. We're going to talk about cardiovascular in a moment here. We got to. These are the things that were, are, are taking a big toll on us because, for example, the plastic story. Let's just talk about that for a second. In the heart, the big study from Italy, multiple centers where they took the carotid artery plaque at the time of surgery and they looked to see if there was plastics, microplastics, nanoplastics in the artery plaque. And they found it in over 60% of people. And that artery under the microscope was grossly inflamed right around where the plastics work.
Dr. Eric Topol
During follow up, was it a dose response? Like in other words, the more plastic.
Mark
The more plastics, the more vicious inflammation. And what was even worse is the people who had the plastics followed versus those who didn't have plastics in their, in their plaque had a four to five fold increase of heart attacks, strokes and death compared to those without the plastic that was basically establishing residence in their arms arteries. And so as we talk about cardiovascular now, preventing heart disease, you know, we gotta factor in that particular thing because you know, plastics are everywhere. They're, they're not degradable and they were just, you know, more and more of them, we got to do something about it. But for the heart, this is where.
Dr. Eric Topol
I want to just, I want to double that. Before you get in the heart, I want to just double click on this because you know what you're saying, people go, yeah, talk to them about it. To have a traditional physician who's got the credentials that you have saying that toxins are something we should pay attention to is near heresy when it comes to traditional medicine. It's something I've been talking about for decades because I've seen it.
Mark
Yeah.
Dr. Eric Topol
And when you look for it, you see it. Even when you look at the literature, it's been there, it's just been ignored because doctors don't know what to do about it because they go, okay, well you do your exposure by doing this and that, the other thing. But this is something that I think is going to be an important thing to be investigated. How do we measure our toxic, toxic load? How do we start to help the body detoxify by supporting its both internal detoxification systems like the liver and the kidneys and the colon and the skin and Sweat, all the things. How do we actually help the body detoxify? And what are novel methods of detoxification that we might want to think about when it comes to these compounds because they're everywhere and we're all polluted.
Dr. Mark Hyman
I think you're right.
Dr. Eric Topol
They do pollution play a huge role in all these diseases of aging.
Mark
You're right. I mean the dirty air and the dirty water, what the things we drink. So the plastics of course are pervasive and we can do some things at an individual family level. You know, in terms of not having things stored in plastics. And like the worst case scenario is you take something food that you have in plastic and you put it in a microwave. It's like oh that's terrible. Microwave microplastics. You're going to eat at you know, to the fourth power. Right. So there are some things we can do and you know just to everything we can to avoid the use of plastics. But you know this is, this is something we're not addressing and that's where the data are so incredibly strong. And air pollution, what are we doing about air quality? Because the air quality these, these fine particulate matter 2.5 and smaller. They are the, the real incriminated, they're the culprits for inflammation, big time increase in inflammation. And you know, you for example, we have now young people and we're going to get to cancer. I don't mean to divert it from cardiovascular because that's my true love. But the, the young people with cancer. Why are people in their 20s and 30s presenting with colon cancer, breast cancer and other cancers like we've never seen before. Who you know what is the. Could it be the ultra processed food that they eat high amounts? Could it be these environmental toxins? Could it be you know the cumulative of all these things. But something has got to give there because we're not, you know, we're not protecting our young people. And we're seeing much more a real spike in, in cancer. These are age related diseases we're actually seeing in young people which is just horrible.
Dr. Eric Topol
You know this literature around toxins been around and even in heart disease. I remember reading a paper, I think it was the American Journal of Cardiology years ago where they looked at anybody who had lead levels over 2 which is considered normal because level in the reference range is 1 to 10. But there's, there's the normal level of lead is zero in the human body. Like it required mineral that their risk of having a heart attack was higher or as high as those who had elevated cholesterol and an increased risk of strokes. And it was, it was a big risk factor. And it was 39% of the population that had a lead level over 2. Because we live in a world where there's coal burning and, and, and lead levels in the soil and stuff from, from his historical exposure. So you're right. I mean, this toxin story is a big rabbit hole. But, and, and I've written a lot about that and I talk a lot about it, but I think there's a lot of ways people can reduce their risks and reduce their exposure exposures and not be crazy. But there's, there's ways to mitigate it and to help your body eliminate the toxins. So I, I agree. So let's talk about the, the hard part.
Mark
Yeah.
Dr. Eric Topol
Because people say, well, that story's been told. You know, we've got statins, We've got this PC, SK9 inhibitors. We're all good. Like, what's the big deal? What should we worry about? It's just all about LDL cholesterol. What's new?
Mark
Yeah.
Dr. Eric Topol
What, what should we be looking at? What should we be thinking about? And, and, and why. Why are we still seeing so many people with heart disease?
Mark
Yeah, it's still the number one killer around the world, not just here. And it's still the number one killer in women who, you know, they think that it's breast cancer. No, no, it's. This is it. This is exciting because we do know the things that we've been reviewing for risk factors. But we have a way to now establish the risk. Are they really high risk without. Before they ever have heart disease, 20 years plus. And where we do that is we can get simple lipid panel, add the lpob, so a little more than what is the standard lipid panel. The LP will be part of a lipid panel in the next year or two. But anyway, when we get that lipid panel, which is again, very inexpensive, and we can also get a polygenic risk score. Very inexpensive. We can also get a heart clock. Right. And we can get inflammation markers. Anyway, now you have the full stack with your records and you know, and you have somebody who is well before they've ever manifest heart disease, and you say, oh, wow, this person is really high risk for heart disease. What do we do? Well, you get their LDL down, you know, not just to below 70. We go down to 20 or, you know, less than 30. Right. We have so many ways to do that now. We have these injectables that are against this PCSK9, we've got new drugs, five new LP drugs that are going to be out within the next year or so that are really.
Dr. Eric Topol
And we've had none of them. None till now.
Mark
Yeah, we never had one. We always tell, Too bad your LP is over 100. You know, nothing we can do. We're going to be able to change that and that's going to have a big impact. We can get all the inflammation, get all over it. Right. In terms of bringing the inflammation down, we've already seen how GLP1 drugs do that before any weight loss. So that should work well in people who aren't even obese. And we've seen how that can prevent heart preserve ejection fraction heart failure, which is half of all heart failure. Right. GLP1s prevent that. So for heart disease, we're seeing some really breakthroughs for the treatment, particularly the new target of LDL that we have five different drug classes, statins you've mentioned. But the PCSK9, we have three different ways to do that. Now we got other new drugs that are coming. Just recently, the CETP inhibitor worked really well on top of. So we got, we can stamp out inflammation. The other thing is we have a metric we never had before, which is AI. And by the way, that also goes with Alzheimer's. You can do a retina AI examination. So you have a picture of the retina and you do AI on it and it tells you when you're going to have Alzheimer's, if you're going to have Alzheimer's, five to seven years in advance. The retina also tells if you're going to have heart disease or a stroke in advance. It will even tell if you're going to, you know, your calcium score of your heart arteries through your retina. Remarkable. And we should, that should be widely available. It isn't yet, but it will be. We'll be doing smartphone retina check someday. Right. But here's where we get a real kick on a jump on this because if you are concerned about high risk and somebody is say 40, 50, they have significant risk factors. You can do a CT angio, which is now becoming very inexpensive and you can look at inflammation in the artery. I go through this in the book. Inflammations in the artery without a narrowing. Okay. So the, the. It basically does AI of the fat around the artery and it. And this is something that was developed in the UK and it's now getting ready for FDA approval. This is a big jump because we always were.
Dr. Eric Topol
So this isn't the clearly scan. This is something else.
Mark
No, no, clearly. And the other ones in the U.S. don't do this. But this is a, a Oxford University of Oxford spin out. I think it's called Karista. They're going to have that available soon. And I went through the data in the book. I mean they've had multiple papers, but it's striking. If you have inflammation without a narrowing, it's, you know, you could have 15 fold risk of a heart attack. So that's when you use that as a metric. Just like we were talking about the P Tau 217 for Alzheimer's. We've got all these new things for cardiovascular. We are going to get a grip on this and we got to, you know, ideally start early. But you know, the lifestyle factors work really well. This is the most preventable known of the three big age related diseases through lifestyle.
Dr. Eric Topol
Because even without a lot of the drugs, like the lifestyle plays a big role. Like you know, I've seen data up to 90% by healthy diet, exercise, stress mitigation, sleep. Right.
Mark
Yeah.
Dr. Eric Topol
I mean is that, is that in the book?
Mark
I found all these studies that I was really struck by that are recent that showed that if we practice the lifestyle factors that we've been reviewing with the details that we just, we discussed, that gets us seven to 10 years of healthy aging without one of these age related diseases. I mean, who wouldn't want seven to 10 years of healthy aging just from the stuff we've been discussing without any, you know, magic potion or pillow. So that's, I think people don't know about that. I didn't know about that. It's really impressive.
Dr. Eric Topol
That's powerful. So, so what you're saying is some of the advances in cardiology are more pharmacological that you're thinking are coming. Like the drugs that lower this genetically determined lipoprotein called Lp, which I've been checking for 30 years. Apob which I've been checking for 30 Years. I read some article the other day that was like, there's this great new test that can be more predictive of your risk of heart attack than any other test is just discovered. I'm like, what is that? I'm like, look, click through the article. It's like apob. I'm like, oh God.
Mark
I mean you only need to get it once and then you can tell that if you need to check it further. But you're getting at a key point here is it isn't just that we have better, you know, more armamentarium of drugs, but we didn't know how to get the risk down. You know, we didn't know how to say this person's really high risk for atherosclerosis because we didn't really have. We didn't use the polygenic risk score. We didn't have, as we do now, we're going to have a heart clock. We. So there's a big debate out there, as you probably know. How low should we go on ldl? Should we pull out all the stops? Well, if you look at all the data, the lower you go, the more protection. But you don't want to necessarily give people, you know, ezetimibe and statin and injectable and all these things unless they really are at high risk. Then you go for broke and you also get the LP and you get the inflammation down. We have ways that we can do that and we're going to keep having better ways. So this is a striking. It's a combination of who's at risk, the partitioning of risk, and having a better ways to work on that risk.
Dr. Eric Topol
Just to play devil's advocate, because this conversation comes up all the time. You're a cardiologist, so your favorite organ is the heart. And so your idea is get the LDL as low as you can, but your brain is made up of a lot of.
Mark
Only in people who are at high risk.
Dr. Eric Topol
In people who are at high risk. Okay, so if you're a really high risk, but like, what, what about the effects, for example, on the brain and cognitive function? Because the, you know, cholesterol is a big part of your brain and sex hormones, which is what your testosterone is made from, is cholesterol. So how do you kind of navigate that? And what's the truth then? What do we know?
Mark
Yeah, I mean, the statins are probably the most studied drug class in history. Really. Some of the data that comes out of these big meta analyses which say, oh, people don't get any leg cramps. That's not true. You and I know that's not true. People do get severe leg cramps where they can't even sleep at night, you know, and, and all sorts of other, you know, leg and muscle related symptoms. Now, with respect to cognitive and sexual dysfunction, the data really don't show a hit there at all. And in fact, you know, I think that we have some data to suggest the chances of having dementia in people. And Alzheimer's, as, you know, accounts for 70% of dementia, that if you, if you don't have the LDL lowered to, let's say less than 100, less than 70, you're going to be at higher risk for dementia. So if anything, the data support statins and, you know, the data for sexual dysfunction, it's again, some of that's vascular. And if it's vascular, we're talking about atherosclerotic. And that, again, is going to be ameliorated with. And of course, we don't have to just rely on statins. A lot of people do have side effects from statins, no matter what. The group at Oxford keeps saying that everyone can take a statin and it's just, you know, it's mental if they can't. That when I wrote a. When I wrote an op ed in the New York Times like a decade ago, and I called out the diabetes or statins. Okay, because if you take a very potent statin, you have a higher risk of developing type 2 diabetes, right?
Dr. Eric Topol
Yeah.
Mark
Oh, did I get slammed by my cardiology colleagues for that? I said, well, wait a minute. That's the data, folks. I'm sorry. And over the years, we've seen many more reports about, you know, the potent statins, high doses, where you get a higher risk.
Dr. Eric Topol
Yeah.
Mark
And you know what? Most physicians are not keeping up with this. They're not watching their patients to see if their glucose, glycohemoglobin, you know, A1C or fasting glucose. And this is bothersome to me because that is a side effect of statins, particularly potent statins. So again, this is important because if we're going to lower LDL and pull out all the stops and, you know, high doses of rosuvastatin Crestor or atorvastatin Lipitor, that could also raise the risk of that person developing type 2 diabetes. We don't want to do that. And we have cardiologists, my colleagues, they are, you know, really sold on statins, and they basically ignore this, this diabetes issue. And did I ever take grief?
Dr. Eric Topol
I agree with you. And I think there's a concern I have around its effect on mitochondrial function. And some of the data I've seen that even in people without muscle pain, even without elevated muscle enzymes, that there's mitochondrial damage on muscle biopsies. And for me, mitochondria are so key to healthy aging in the brain, in everything from Parkinson's to heart disease, diabetes. Diabetics have poor, poorly functioning mitochondria that may be part of why it causes it. And so I'm wondering some of these other drugs that are coming down the pike, even though Some of them are expensive. May be a better solution.
Mark
Well, people that have clear cut adverse effects, the PCSK9 injectable drugs are a winner because they're potent and they have not been associated with diabetes, which is really interesting. They have not been associated with cognitive or other side effects. So most insurers cover that now. We, you know, went through years where it was a. Because they were so expensive, the cost has come down. So as long as people have the right indication where they have significant side effects or they need to have their LDL substantially lowered, it's usually not a financial stress for most people.
Dr. Eric Topol
So heart disease still it's lifestyle, but then there's a cocktail of other drugs in very high risk patients that you can detect early to figure out. And, and what about lipoprotein fractionation which is a lab test that we include as part of function Health as well as APOB and LPA, something I've been testing for 30 years. But do you think that's as important? Because to me the particle number and particle size story is important and it's a sort of a clue that there's insulin resistance, which is one of the biggest drivers of heart disease and all the other age related diseases.
Mark
Yeah, I mean, I think it's mild, potentially mild incremental information. I just don't see that it has nearly the impact of just zeroing in on LDL and lp. And I do recommend that everybody get an APOB at least once and then you can figure out whether that needs to be further assessed. These other things, you know, it's an additional expense. I just haven't seen the value. But you know, I have colleagues that are lipidologists that test every known particle in the mankind.
Dr. Eric Topol
Right.
Mark
I just haven't, I haven't really seen the benefit because it doesn't change. Usually to me I got to know the person's risk and then I'm going to go after inflammation, I'm going to work on their lifestyle and if necessary, you know, get their LDL down as low as possible. So the other things just don't have a, for me a added value. But I do know there are people that are, you know, wild and crazy on every particle. Small, large, dense, you know, you name it out there.
Dr. Eric Topol
Yeah, yeah, so I hear you on that. I think it's, you know, sometimes more information isn't always better. But you know, then what is the most important information? I think you cover that in your book and I think, you know, we're going down the kind of the horseman of the apocalypse. You know, the heart disease, the cancer, the dementia. I think diabetes is sort of all in there and related. But you're talking about how there's kind of a newer, with the advances in our diagnostics, whether it's imaging or retinal scans or new ways we can measure dementia, biomarkers that we never had before. Cancer, we'll get into in a sec. That these diseases can become more optional, like they're not inevitable. We have more agency than we ever had before given what we know now. And when you layer up what we're learning with AI and using multimodal treatments, we're really able to actually make a big dent if people really understood how to navigate this. And the sad part is that you spend your time thinking about what's coming. Most physicians are just trying to deal with the onslaught of what is and don't have the bandwidth to actually apply this stuff until it kind of is way often decades later. And so I really appreciate your sort of paying attention to what's happening and keeping your nose the scent of where things are emerging because otherwise people just don't know. And doctors, like you said, don't know. And, and the average person doesn't know. But this is such a hopeful message. I want to kind of finish on, on cancer because I think this is one of those things that, you know, the C word, you know, nobody wants to get that diagnosis. It's very scary. Most cancers are picked up late stage.
Mark
Yes.
Dr. Eric Topol
When this five year survival rates are very low in the 5 to 20%. If that. And picking things up early and understanding your risk can, can lead to cures essentially. Like, and I think with. What I'd like to hear is your sort of perspective on this with new liquid biopsy testing, with, with new, new technologies of imaging, with new, you know, maybe other proteomics that are coming. What, what is, what is out there that's emerging? Because you know, my sister died of cancer. 57. My dad died of cancer. He was otherwise really healthy. He'd been a smoker when he was younger, but quit and ended up getting lung cancer. Like they could potentially even still be around if, if they hadn't died of cancer. And, and I don't want to get cancer saying I'm with you.
Mark
Yeah. My, my mother died of cancer in her 50s and most of my relatives on my father's side had colon cancer. You know, I've had a lot of cancer in the family for sure. And I agree no one wants to go through this and I do believe we Have a path to prevent cancer, and certainly it's spread, right? If you can find it microscopically, which we don't right now very well, long before it's ever shown on a scan. And once it's on a scan, if it's really cancer, you're talking about billions of cells, right? You want to find it if it does exist microscopically. So why is this such an exciting area? Again, we can find through the full stack who's at risk and for which cancer. And so we have a way, you know, whether it's polygenic risk or genome sequence, we can do, for example, you know, just looking at the clocks, which is another way to get a window into a risk of cancer. If a person has a significant risk and, you know, family history is part of that, right. Then they also confirm through these other. I mean, a simple polygenic risk will tell us a lot. This is now a different story completely, mark, than the way we screen for cancer today, which is as dumb as it could possibly be. Age 50, you show up women, mammogram, right? All right. Only 12% of women in their lifetime will ever have breast cancer. 88% will never develop breast cancer. But they're all supposed to get mammography on a frequent periodic basis starting age 40, 45. This is, you know, crazy. We don't do anything to partition risk. The same for prostate cancer, colon cancer. You name the cancer. This is what we do. We treat every human the same. We waste all this money on mass screening. Right now, what I'm suggesting is let's partition people's risk. If they're high risk, then they should have screening. But that screening is different. It's basically establishing the risk. And then if we see a person, you know, as a significant risk, you can then do a plasma tumor DNA assessment, right? That right now, is pretty expensive. It's 800, $900. The one that's used the most is gallery of. Of Grail. And almost 400,000 people have had that test. But guess what, Mark? The people who've had the test is because they're age 50. I mean, that's the plus. That's not the reason they should get the test. It should be because they have risk of cancer. Anyway. The yield for that test is very low, and most of it is already late stage. Two out of thousand, you might pick up an early cancer. So you got to use the test right in the right people. This is something I can't emphasize then. That test and all the other liquid biopsies have a much better Chance to be helpful. So we have that. But also this is where our immune system kicks in. Because we don't have that immune system metric. System metric, except for immune clock. But if we did, you know, if our immune system was amped up, we wouldn't have cancer spread, we wouldn't see metastasis.
Dr. Eric Topol
It was surveilling. Yeah.
Mark
You know, what we know is this. Some people. This is really fascinating. Some people will have a positive test for tumor DNA and they reassessed in a few months and it goes away. What do you think happened? Was it a false positive? Did that person's immune system kick in? I think what we're learning is it's the immune system. And what we have to get is this is the missing piece right now, the immunome. If we can get this and find people who are at risk for cancer and just make sure throughout their lifetime that their immune system has got good integrity and it can fight off the threat of a cancer of a foreign protein that would be on the antigen, on the surface of the. Of cancer cells. So I am really gung ho, because if you look at the treatment of cancer, we're now seeing things we've never seen. Personalized NEO antigen vaccines to cure pancreatic cancer, to cure renal cell carcinoma. Intractable, that is people that failed everything else. The other thing just to mention here again is AI. We are seeing AI used for the electronic health record using the unstructured nodes and the regular nodes and set points, that is the lab values. But even when they're in their normal range, AI analyzes. Oh, it's even in the normal range. And we look at it, say there's no asterisk. So it's okay. Well, no, the AI is. This is flagging a risk of pancreatic cancer. This is flagging a risk of ovarian cancer. The hardest diagnosis of cancer we're seeing that can be brought much earlier through AI of all of a person's data. We saw it from the study that was done in Denmark in the VA for pancreatic cancer. We're going to see Sloan Kettering has.
Dr. Mark Hyman
But what were they looking at?
Dr. Eric Topol
Because they weren't. They were looking at tumor markers where they were looking at regular blood tests.
Mark
Yeah. So they looked at a person's nonspecific symptoms, like, you know, abdominal symptoms for pancreatic cancer. And they saw abnormal. They saw ranges of liver function tests in the normal range but trending in the wrong direction. Right. So yeah, the AI picked up the higher risk of people that we might not, we, we might discount. These are non specific symptoms. These tests are lab tests. They look normal, but they're not normal when you are looking at this in serial assessment. So I'm also lots of different ways that AI is helping to us to gauge a person's risk and help us to pick up these occult, difficult to diagnose cancer.
Dr. Eric Topol
I mean, this is so important what you're saying that there was a paper in Nature Medicine recently on personalized lab data and the idea was that exactly what you're saying, that even though it's quote, normal, it may not be normal for you because if you were 20 and it goes up to 35, which is still in the normal range, that might not be good.
Mark
That's right.
Dr. Eric Topol
And we need to start getting a baseline of what our data is and tracking it over time and having AI help us learn from it. Because, you know, as a doctor, you see thousands of patients that come in and you know, they have their lab panel every year. You can't keep in your mind what their liver function tests were last year or five years ago or ten years ago and how that differs and how that, what's the variation from their normal or baseline test. You can't, you can't do that as a human being. Right. And I mean I have certain patients who are OCD and they bring in spreadsheets with years and years of their data and you can graph it all. And I'm like, wow, it's like I never saw that before. But without that, you really don't know what's going on.
Mark
That's the paper I was talking about on set points. Exactly what you're. Yeah, and we just don't look at that because if it's normal, we don't look at, you know, the last few years, how things are just, you know, inching up. And that's what, that's the way AI can help us. And it is helping. We've already seen proof of it. So for a variety of conditions, but especially these three age related disease and especially cancer, because we are not doing well with cancer. You, you said it. We're only diagnosing cancer when it's way too late. And that's got to change because when it's picked up first, picking up that this person has risk and picking up when it's microscopic well before you ever catch it on a scan. That's why, you know, I'm not, I'm not keen on these, you know, total body MRIs because they're being used to Pick up already a cancer that's got a mass. Right. And of course a lot of times it's not even cancer, it's benign and people go through unnecessary biopsies. But I do think if a person's high risk and certainly if they have a positive liquid biopsy, you know, tumor DNA, then it's a very reasonable thing to pursue. We're going to do much better. And all these years of trying to treat cancer and cure it, you know, what do people have to go through to get there when you could prevent it? And you know, I think this is where we have a brilliant future. It may take a while to get it implemented, but it's ready to go.
Dr. Eric Topol
In many respects, just to go a layer deeper. So just you talk about polygenic risk for cancer and, and we've heard about the BRCA gene or familial polyp disease, increased risk of cancer disease. Those are unusual. Although they're things you can measure and track. If you have a family history, you're talking about a different set of genetic biomarkers that are being discovered that help us segment people in terms of their risk related to different cancers.
Mark
Yeah, so you're bringing up the rare mutations, but for example, they can all be had in a sequence which costs a couple hundred dollars, a full whole genome sequence. And BRCA2, we as men, you know, we're a lot of, a lot of us carrying a BRCA gene just because we don't have breast cancer, you know, that means we have a higher risk of prostate cancer ourselves and other forms of cancer. So you know, these, these are pathogenic genes. And I go through that BRCA2 story in some depth because of the Icelandic data where it made a difference of up to seven years of healthy aging, mainly because of cancer. Now so you get these rare so called pathogenic genes that have a high risk of cancer, but you also can get a whole bunch of susceptibility genes. So they're not this high deterministic, very like we were talking about APOE 42 copies, but they are increasing the risk. So what you have are three different types of gene markers. One is the rare variants like BRCA2, BRCA, BRCA2 and as you said, lynch syndrome and these other familial polyposis. The next is the common variant, the common variants, which is what you pick up in a usually like say 200, 300 gene variants that would give you the high risk for breast cancer. Cancer. They're not brca. These are just common variants that you got to admixture from your mother and father. Right. And then the third group are these other susceptibility genes that can be gleaned from a genome sequence. When you have all that data, which is again not expensive and processed properly, then you know if what type of cancer you're at risk for, if you're at risk for a cancer, it doesn't tell you when, it just says yes, no. Right. That's the when is when we have to, you know, get early, get on this early and not, not treat everybody who's 50 and older as if they were, you know, a cattle, that we're all the same. We have to be much smarter about this.
Dr. Eric Topol
This is what we call precision medicine or personalized medicine where it's very. And then we're finally entering the year. I think AI is going to help us get smarter about that. The other thing, you know, you sort of mentioned was sort of liquid biopsies and you kind of touched on this a little bit. But proteomic kind of testing, the liquid biopsy, from what you're, I hear you saying you don't think it's a good screening tool because it picks the things late, but if everybody got it, it would pick up things earlier. Right. If it was sort of cost was down and scale was up for blood tests every year with your checkup, you could potentially be picking up stuff much more frequently and much earlier. Right?
Mark
Well, potentially. But you see it's not being, it's just being done, you know, for, on the age criteria. And the yield of picking up an early cancer is 2 per thousand people, which is really, really low. Right. That doesn't make it.
Dr. Eric Topol
Unless you're one of those two.
Mark
Yeah. I mean, and also, you know, if you had the test and it's negative, that doesn't put you in, you know, in the safe zero risk group. Yeah. It's only if it's positive where it's really helpful. I do think these tests are going to get better. There's lots of ways. You know, this is a very minimal amount of tumor DNA in the plasma and there's ways to jack that up to make the test better. And as you got to, it's got to be cheaper. But yeah, again, this whole base theorem of don't do tests that are not in people who are healthy of no risk, but when you do it in people like the 2 per thousand I cited is in healthy people age 50 plus. But if it was done in people who were, you know, clearly had increased risk, that yield of picking up, then.
Dr. Eric Topol
It'S a better test, yo.
Mark
Yeah. And also when you're paying $900, that's, you know, substantial. If we get that test down to $100 or something like that, and it's more sensitive, more accurate in the right people, it's going to become very commonly used. So you're heading down the right path with that point. Yeah.
Dr. Eric Topol
And then the other thing I've been hearing about is proteomic tests where common protein, some of the common proteins we look at for cancer like CA125 or CA99 for colon cancer, like they're combining that with multiple other proteins and they're able to kind of using AI to predict that you'll be able to pick up these cancers much earlier with these proteomic signatures that they have in the blood, which are really inexpensive to do.
Mark
Right. So that's Johns Hopkins Burt Vogelstein effort. And that's right. As you said, they combine some key proteins that have been established as markers with some gene variants and made it a relatively inexpensive test. And that's one that certainly has a potential as well. We're going to be able to do so much better with the screening using, you know, the blood, because once it shows up in the blood in a microscopic, that's when we, you know, get all over it. Because this is, I think, a new era of early diagnosis. It's essential. And we just, you know, again, you get it on a mammogram, it's already got a problem, you know, and yeah, we're not even using AI in this country for mammograms routinely. And we should. That's the best AI case that exists today. 100,000 plus women in Sweden, they picked up 25% more cancers and compared to radiologists alone, you know, significant cancer and no increase in false positives. Why aren't we using that? So we're not doing a good job here for cancer screening or partitioning risk, no less upgrading it.
Dr. Eric Topol
I mean, you mentioned imaging a little bit, but my understanding is that with new AI, advanced sort of interpretation and stuff, that with these more high resolution scans, you can pick up cancers down to 2 millimeters, which is pretty small. It's like basically the sign of a ballpoint pen.
Mark
Yeah.
Dr. Eric Topol
And, and at that point they're not likely to have spread or metastasized. And then, you know, you can see changes over time if you do serial imaging. Seems to me that's a, that's a kind of a useful tool, might be, and it may pick up things that are more sensitive than the gallery, which is not as sensitive.
Mark
Yeah, it might be. I think what we've seen at least unequivocal, you know, a huge trial is that AI of a regular mammogram. Not like you're talking about, not ultra high resolution. It can really make a difference. And so that I think is, you know, we should be implementing that and we're not. And it's just, you know, we're missed opportunity. There's a big study that showed that if you have AI analysis of a regular mammogram, you can predict cancer from that in that woman five years ahead if they're going to develop cancer. So the AI of SCANS continues to see things that we humans can't see. And the fact that you can look at a mammogram with an AI not only make the diagnosis of cancer more, you know, better than radiologists alone, but also see some patterns that indicate the person's much higher likelihood of cancer in the next five years. So it's just like what we're talking for about with the ability to predict the other age related diseases.
Dr. Eric Topol
Yeah. So the, and the fourth thing you said was really around finding ways to enhance our own body's immune function.
Mark
Yeah, yeah.
Dr. Eric Topol
Like natural killer cell function. I know Patrick Soon Shong is working a lot on this and I don't know, I'm not deep enough into it to know whether there's a lot there to it. But it seems like an interesting theory that if we can see a decrease in our own tumor surveillance with lower natural killer cells, which is part of our immune system, the white blood cells that kill cancer and infections, that we can amplify that effect. That could be a powerful therapy.
Mark
Yeah. So this, there's a whole chapter on the immune system. And you know, after the brain, this is the most complex system there is. There's so many different cells and, you know, interferons and antibodies. But the big thing here is we have ability to control our immune system like never before. Up or down, like a rheostat. Right. And with that capability that gives the confidence that we can amp it up for people at high risk for cancer or at the earliest possible diagnosis. So we're no longer going to give these, you know, toxic drugs, but we're going to just get their immune system in high gear. And also, of course, what we've never seen before, Mark, is by taking people with autoimmune diseases like lupus, systemic sclerosis, even multiple sclerosis, by giving them T cell engineered T cells car T directed towards depleting their B cells that when the B cells come back they forgot that the person has an autoimmune disease. They have a control alt delete. I mean this is incredible right that they no longer and for now 37 years of follow up they're cured of an autoimmune disease. We had never seen anything like that before. And of course you know we're seeing you know more and more reports of this ability to cure you know, really vicious autoimmune diseases that can you know, killers and no less really severe morbidity. So that is another besides the cancer immunotherapy which is huge. I mean you, the fact that we. The more you give immunotherapy higher gear high the more chance you are going to be able to treat successfully a person with an intractable cancer. So between all these things we're learning about the immune system. System no less. The missing metric. The ability to test a person's immune system at any point during a. Let's say their annual checkup or whenever. Once we get that then that's the missing link right now. And then, then we're also.
Dr. Eric Topol
That's the protein clocks. That's the immune age protein clock.
Mark
Yeah, yeah we have an, we have a immune clock but we want more than that because that as you got to early on in our conversation that's, that's a piece of it. But we, we want to know about the T cell story, the B cells, the nk, all these different cells. We want to know about. I do present in the book a kind of first tier immuno that I had of Johns Hopkins startup called Infinity Bio where I had all my auto antibodies. Every virus I've ever been exposed to in my life. Interestingly you know, I never had been exposed to CMV and all sorts of things that are going to helpful and, and this could be done inexpensively. It will be common. It's all part of this immunome that we don't have right now that we.
Dr. Eric Topol
Need to loop back on the cancer thing. But before I go that you mentioned T cells and measles. People probably don't know but you know B cells are the ones that create antibodies and autoimmune diseases are where you make antibodies against your own body's tissue. So that's why it's so important. And T cells are more of an ancient part of your immune system that are more general and, and, and are we call cell mediated which is different than antibody mediated. And those will basically turn off the B cells so that you don't make antibodies. That's kind of cool. I didn't know about that.
Mark
Yeah. These key regs that are the key T cells that you can, you know, get to tone down your whole immune system. And then, you know, and then killing this. These cells that have the foreign. The alien antigen, the cytotoxic CD8 T cells, I mean, so we. The immune system we have is rich. The problem is, as we get older, you know, it lets down. And in some people more than others. And we have to be on top of that. That's the one thing that if you had to go back and say, the elderly, how did they get there? Maybe some of them, it was just, you know, random stochastic luck. But for the most part, these people are, you know, they got a great immune system that just carry them through. And we want everybody to have a great immune system someday.
Dr. Eric Topol
Good. And I think we're going to learn more about how to do that. Just to kind of go back to the cancer story, I just want to finish summarizing it, because as I think about all these new technologies, whether it's, you know, collections of genes that put you at higher risk that aren't a cancer gene, but that, you know, collectively increase your risk, combining with the liquid biopsies to get more and more accurate at less of a cost, combined with protein signatures of different cancers that can be picked up way before you'll see anything in any other test, combined with better resolution, AI imaging done serial over time. It seems to me that you can't prevent us from getting cancer because we live in a toxic world and there's shit that happens. But we could make dying of cancer a historical footnote.
Mark
Oh, yeah? Yeah.
Dr. Eric Topol
Is that fair to say?
Mark
Yeah. I mean, what we have to do. And I go through this in the cancer chapter in the book, we have to prevent metastasis because people don't die of the cancer per se, they die of the spread of that cancer. And if we can just get rid of metastasis, which we can, There's a way to do this now, then that's going to be our big dent in the cancer story. And, you know, obviously we want to even catch it when it's. Before it gets to microscopic. And we put people under surveillance who, once we determine they're at high risk. But I think what is so exciting here is just prevent it ever getting legs if it doesn't spread. We got a winner strategy here.
Dr. Eric Topol
You and I can geek out on this all day long. I think we didn't get to a lot of things I did want to talk about. But we covered, I think, some of the most important things, which is the advances in medicine are happening so rapidly that we're learning about ways to detect early, very early, far early than we used to, and to be proactive with what we learn about through lifestyle and other novel therapies, that we can make these three horsemen of the apocalypse kind of not so scary anymore. Heart disease, cancer and dementia.
Mark
Yeah, I mean, that's the nuts of it. I think what's so exciting, and you know, why I'm so optimistic, is for millennia we talk about preventing these diseases and we never did it. And now we can do it. We can do it. It wouldn't happen if we didn't have the science of aging metrics. We've been discussing these new ways to track a person, you know, really accurately and temporally. And it wouldn't happen without the multimodal AI to assemble, integrate all the data at the individual level. So it's these two things coming together that's made this possible. It's a unique, really momentous time. And that's why I'm so optimistic that we can make a difference. This will be the chance in medicine to finally fulfill that fantasy of primary prevention.
Dr. Eric Topol
And really, at the end of the day, it comes down to creating large data sets on each individual. So learning about all your biomarkers and data, from genetics to proteins to lab testing, to be able to understand the root causes and the risks, and then using AI and big data analytics to actually make sense of it all through the lens of our new understandings of human biology and systems biology. And to me, that's, to me, so exciting because we've been sort of just playing reactive medicine for so long. And yeah, this, this is a time when we can move towards more proactive medicine. And I think doctors would be happy about that if they, they can figure out, if we can figure out a way to make them do their job in a more sort of streamlined, easy way that makes this accessible to them and to their patients. It's going to be a game changer.
Mark
Yeah. I mean, you know, we've been banking on find cures, and that's much harder than prevention.
Dr. Eric Topol
Yeah.
Mark
And, you know, a pound of this is a win. This is a winning plan. If we get serious about it, we can really do something.
Dr. Eric Topol
Well, that's exciting. I need, I think everybody needs to check out your book, Super Agers. It's quite, it's quite a story. It's a little more sort of technical than maybe most people would like. But there's ChatGPT. You can look up stuff you don't understand and, and I think that this, this book is the potential really change our thinking in medicine. I really enjoyed it and I'm really grateful for you being so curious. You're like Curious George, I think. Thank you for your curiosity. Thank you for all the work you've done in medicine for so many years and hope we get to chat again soon and get you back on the podcast and we talk about some things we could talk about.
Mark
I just would add I tried to get it as simple as I could for everyone to understand and there are some parts that get a little dense. I apologize early in the book for that. But I think there's a lot of things in there that hopefully everyone can understand. And I did do the reading so that people, they don't have to, you know, read it. They can just do the, the audio, hear the passion and all that. And finally there's 70 some graphs in there. So a lot of times people can graph, grasp the graphs and so hopefully your point is a good one because you know there's a lot of 1800 citations so there's a lot there. Hopefully the people will, will get something out of it.
Dr. Eric Topol
I know I'm going to see you well over 100 years old.
Mark
I hope you're right. And vice versa.
Dr. Eric Topol
If you get to 100, invite me to your birthday.
Mark
I just want to get to whatever age and say as long as I can to meet that kind of welderly criteria of plus 80 plus and no age related major diseases that we've been discussing.
Dr. Eric Topol
I think that's a take home. Don't end up being elderly. You can be welderly by just following this advice.
Mark
We're going to get there a lot more elderly in the future. That's what's in store.
Dr. Eric Topol
Thank you. All right, well, thanks so much Eric.
Mark
Thank you.
Dr. Eric Topol
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Dr. Mark Hyman
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Title: How to Catch Alzheimer’s Before It Starts, with Dr. Eric Topol
Host: Dr. Mark Hyman
Guest: Dr. Eric Topol
Release Date: July 23, 2025
In this insightful episode of The Dr. Hyman Show, Dr. Mark Hyman engages in a profound conversation with renowned physician and digital medicine expert, Dr. Eric Topol. Together, they explore groundbreaking advancements in the early detection and prevention of Alzheimer's disease, the interplay between genetics and lifestyle in longevity, and the transformative role of artificial intelligence (AI) in modern healthcare. The discussion also delves into broader health concerns, including cardiovascular disease and cancer, highlighting the potential to redefine disease prevention and enhance overall well-being.
The conversation opens with Dr. Topol inquiring about the earliest markers of Alzheimer's:
Dr. Eric Topol: "When you start talking about preventing Alzheimer's and picking it up early, how early can you start to see the P Tau changes?" [00:02]
Dr. Hyman responds by emphasizing the significance of the P Tau217 biomarker:
Dr. Mark Hyman: "P Tau217 is the very first one that goes up and it starts 20 years before mild cognitive impairment. 20 years." [00:11]
This revelation underscores the potential to detect Alzheimer's two decades before clinical symptoms manifest, offering a crucial window for intervention and prevention.
Dr. Topol shares an anecdote about a patient with a high genetic risk for Alzheimer's who remained cognitively intact into her 90s, illustrating that genetics alone do not determine health outcomes.
Dr. Hyman elaborates on the Welderly Study, a seven-year research project involving 1,400 individuals aged 90 to 102 who had never experienced chronic diseases. Contrary to expectations, the study found minimal genetic variations responsible for their exceptional longevity, pointing instead to robust lifestyle practices.
Dr. Mark Hyman: "This is also consistent with so many of these people had relatives... it isn't a genetic story." [06:06]
This finding offers a liberating perspective for individuals with a poor family history of chronic diseases, highlighting the profound impact of lifestyle choices on health and longevity.
The discussion transitions to the immune system's pivotal role in combating age-related diseases:
Dr. Mark Hyman: "Our immune system is so critical and that is giving us that resilience to withstand the threat of age-related diseases." [08:23]
Dr. Hyman introduces the concept of immunosenescence, the gradual decline of the immune system with age, and emphasizes the need for comprehensive metrics to assess and maintain immune health.
Dr. Topol brings up polygenic risk scores, which evaluate multiple genetic variants to assess an individual's susceptibility to diseases without being deterministic.
Dr. Hyman discusses how lifestyle modifications can mitigate genetic risks:
Dr. Mark Hyman: "There are several studies I review in the book of polygenic risk and how that's neutralized by lifestyle factors." [07:43]
This synergy between genetics and lifestyle reinforces the idea that individuals are not bound by their genetic predispositions and can actively influence their health trajectories.
Dr. Hyman criticizes the pervasive consumption of ultra-processed foods in the United States, linking them to systemic inflammation and chronic diseases:
Dr. Mark Hyman: "The ultra processed food are just horrendous... 80% or more." [35:04]
He advocates for plant-based diets, highlighting studies that demonstrate significant health benefits, including reduced inflammation and lower incidence of chronic diseases.
The importance of strength training is emphasized as a powerful tool for preventing age-related decline:
Dr. Eric Topol: "Strength training is a powerful drug and sleep is a powerful drug." [00:38]
Dr. Hyman shares his personal journey with resistance training, illustrating its effectiveness in enhancing muscle mass, improving metabolic health, and reducing the risk of chronic diseases.
Optimizing sleep, particularly deep sleep, is highlighted as essential for brain health and the clearance of toxic metabolites:
Dr. Mark Hyman: "The deep sleep which is when we get rid of the toxic waste metabolites in our brain... I've been able to get over 45 minutes a night." [42:59 – 44:52]
He warns against the overuse of sleep medications like Ambien, which can disrupt natural sleep processes and impair waste clearance in the brain.
Dr. Hyman and Dr. Topol discuss the interplay between mental health, stress, and chronic diseases. Maintaining strong social connections and managing stress are presented as vital for reducing inflammation and enhancing overall health:
Dr. Mark Hyman: "Social interaction... we have to use that ability to help us stay in the mix." [20:13]
Dr. Eric Topol: "The mindset plays a big role... level of gratitude... level of service or engagement or connection." [17:10]
As a cardiologist, Dr. Hyman delves into the latest advancements in cardiovascular health:
Biomarkers and Lipid Panels: Incorporation of LDL, ApoB, and LP(a) into lipid panels for early detection of heart disease risk.
AI-Enhanced Imaging: Utilization of retinal scans combined with AI to predict heart disease and stroke risk years before clinical symptoms appear.
New Medications: Introduction of PCSK9 inhibitors and emerging lipid-lowering drugs that offer substantial reductions in LDL cholesterol without the side effects associated with traditional statins.
Dr. Eric Topol: "The retina also tells if you're going to have heart disease or a stroke in advance." [60:18]
Dr. Hyman critiques the reliance on statins, highlighting their side effects, including muscle pain and increased risk of type 2 diabetes:
Dr. Mark Hyman: "Statins are probably the most studied drug class in history... higher risk of developing type 2 diabetes." [66:07]
He advocates for personalized medicine approaches, leveraging AI and advanced metrics to tailor interventions and optimize cardiovascular health.
The duo explores the detrimental effects of environmental pollutants, such as microplastics and fine particulate matter, on systemic inflammation and chronic diseases:
Dr. Mark Hyman: "They are... air pollution... artery was grossly inflamed right around where the plastics work." [51:30]
The conversation underscores the urgent need for both individual and systemic measures to reduce toxin exposure and mitigate their health impacts.
Dr. Hyman and Dr. Topol discuss pioneering advancements in cancer detection, emphasizing the potential to transform cancer prevention and treatment:
Liquid Biopsies: Blood tests capable of identifying microscopic tumor DNA before clinical symptoms arise, enabling early intervention.
AI-Driven Imaging: Enhanced imaging techniques with AI integration that can detect cancers at sizes as small as 2 millimeters, well before they become symptomatic.
Immune System Optimization: Strategies to bolster the immune system's natural surveillance mechanisms to prevent cancer metastasis.
Dr. Mark Hyman: "We have a way to now prevent cancer... prevent metastasis because people don't die of the cancer per se, they die of the spread of that cancer." [94:43]
Dr. Eric Topol: "AI analyzes... and we look at it... have to track it over time and having AI help us learn from it." [78:25]
These innovations, combined with AI's ability to synthesize vast amounts of data, promise to make cancer a historical footnote rather than a leading cause of mortality.
AI emerges as a central theme, revolutionizing early disease detection and personalized medicine:
Dr. Eric Topol: "AI analyzes... and we look at it... have to track it over time and having AI help us learn from it." [78:25]
Both speakers emphasize AI's capacity to integrate genetic, proteomic, and lifestyle data to provide comprehensive health assessments, enabling proactive interventions and enhancing longevity.
The conversation highlights cutting-edge research on boosting the immune system to prevent diseases like cancer and Alzheimer's:
Dr. Mark Hyman: "The immune system we have is rich... we have the ability to control our immune system like never before." [90:00]
Strategies discussed include:
T Cell Engineering: Innovations in modifying T cells to target and eliminate cancerous cells effectively.
Immune Metrics: Development of comprehensive immune system metrics to assess and optimize immune health regularly.
Dr. Hyman and Dr. Topol conclude on an optimistic note, emphasizing the unprecedented opportunities to prevent major age-related diseases through early detection, lifestyle modifications, and technological advancements. They advocate for a shift from reactive to proactive medicine, harnessing AI and personalized data to enhance healthspan and longevity.
Dr. Mark Hyman: "We can do it... with the multimodal AI to assemble, integrate all the data." [95:15]
This episode serves as a beacon of hope, illustrating how integrated approaches combining cutting-edge science, personalized interventions, and technological innovations can redefine the landscape of health and longevity.
Note: Timestamps correspond to sections of the transcript and are included to reference notable quotes.